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Background frailty is a condition of reduced function and health due to ageing processes and is associated with a higher risk of falls, hospitalisation, disability and mortality. Objective to determine the relationship between household wealth and neighbourhood deprivation with frailty status, independently of demographic factors, educational attainment and health behaviours. Design population-based cohort study. Setting communities in England. Subjects in total 17,438 adults aged 50+ from the English Longitudinal Study of Ageing. Methods multilevel mixed-effects ordered logistic regression was used in this study. Frailty was measured using a frailty index. We defined small geographic areas (neighbourhoods) using English Lower layer Super Output Areas. Neighbourhood deprivation was measured by the English Index of Multiple Deprivation, grouped into quintiles. Health behaviours included in this study are smoking and frequency of alcohol consumption. Results the proportion of respondents who were prefrail and frail were 33.8% [95% confidence interval (CI) 33.0–34.6%] and 11.7 (11.1–12.2)%, respectively. Participants in the lowest wealth quintile and living in the most deprived neighbourhood quintile had 1.3 (95% CI = 1.2–1.3) and 2.2 (95% CI = 2.1–2.4) times higher odds of being prefrail and frail, respectively, than the wealthiest participants living in the least deprived neighbourhoods Living in more deprived neighbourhood and poorer wealth was associated with an increased risk of becoming frail. Those inequalities did not change over time. Conclusions in this population-based sample, living in a deprived area or having low wealth was associated with frailty in middle-aged and older adults. This relationship was independent of the effects of individual demographic characteristics and health behaviours. [ABSTRACT FROM AUTHOR]

Objective This study aimed to investigate the relationships between trajectories of change in self-reported hearing over eight years with subsequent effects on cognition, measured using episodic memory. Methods Data were drawn from 5 waves (2008–2016) of the English Longitudinal Study of England (ELSA) and the Health and Retirement Study (HRS), involving 4,875 individuals aged 50+ at the baseline in ELSA and 6,365 in HRS. The latent growth curve modelling was used to identify trajectories of hearing over eight years, and linear regression models were performed to investigate the relationship between hearing trajectory memberships and episodic memory scores, controlling for confounding factors. Results Five trajectories of hearing (stable very good, stable fair, poor to fair/good, good to fair, and very good to good) were retained in each study. Individuals whose hearing remains suboptimal and those whose hearing deteriorates within suboptimal levels throughout eight years have significantly poorer episodic memory scores at follow-up than those with stable very good hearing. Conversely, individuals whose hearing declines but is within an optimal category at baseline do not see significantly poorer episodic memory scores than those with consistently optimal hearing. There was no significant relationship between individuals whose hearing improved from suboptimal baseline levels to optimal by follow-up and memory in ELSA. However, analysis using HRS data shows a significant improvement for this trajectory group (−1.260, P  < 0.001). Conclusions Either stable fair or deterioration in hearing is associated with worse cognitive function, both stable good or improving hearing is associated with better cognitive function specifically episodic memory. [ABSTRACT FROM AUTHOR]

Background Previous research has shown older adults experience dynamic changes in frailty status. This study aimed to determine the occurrence of sustained frailty remission and how remission is associated with falls risk. Methods Participants who contributed data to the analysis were in the English Longitudinal Study of Ageing from Waves 1 to 8 (2002–2017). Frailty was defined across waves using the frailty index and categorised into robust, pre-frail and frail. We classified participants who improved their frailty category from Wave 1 (2002) to Wave 2 (2004) and sustained/improved category again into Wave 3 (2006) and compared them with those who were either robust or frail across Waves 1–3. Cox proportional hazard modelling was used to determine the risk of incident falls reported at Waves 4–8, with results expressed as hazard ratios and 95% confidence intervals. Results Of 2,564 participants, 389 (15·2%) improved frailty category and sustained this during Waves 2–3, 1,489 (58·1%) remained robust and 686 (26·8%) remained frail during Waves 1–3. During the 10-year period (Waves 4–8), a total of 549 participants reported a fall. Compared with those who remained frail during Waves 1–3, those who with sustained frailty remission had a lower risk of future falls (HR 0·41; 95% CI = 0·36–0·45). Conclusions Frailty remission is possible and can be sustained across 5 years. There is a lower risk of future falls in those who sustain frailty remission compared with those who remain frail. [ABSTRACT FROM AUTHOR]

Individuals with an 'evening' chronotype tend to sleep and wake later than people described to be 'morning' type if given a free choice. Since early awakening times, due to school and occupation, may be more challenging for those with evening chronotype, they are expected to be at greater risk of adverse health, occupational and educational outcomes. Our objectives are to investigate associations between chronotype and occupational, educational and health outcomes in a longitudinal cohort. We use sleep, sociodemographic and health data from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age, 1982 through 2010. The relationship between employment and longitudinal midsleep trajectories were estimated using linear mixed models. Associations between employment status and Cornell Medical Index, Beck Depression Inventory scores, cortisol concentrations at different times of the day stratified by chronotype were estimated using regression. The relationship between chronotype, occupational success, education, and cognition were also examined using regression methods. In older adults, compared to non-employed participants, employed participants get up 0.45 hours earlier. Evening-type employed individuals had earlier midsleep time compared to their non-employed counterparts and had abnormal longitudinal trajectories with an increasing trend as they aged. Employed individuals with evening chronotype had a higher risk of depression than employed morning-types. Moreover, employed individuals with evening chronotype had a higher cortisol concentration at 14:00 h than non-employed individuals. In addition, memory score was lower in individuals with morning chronotype, however processing speed was higher in individuals with morning chronotype compared to evening. Morning-types had a higher age when they finished full time education. Relative to evening-types, those with morning chronotype were 6.5% more likely to be in a job classed as professional or intermediate. Our findings suggest that evening-types are at a disadvantage with regards to occupational, educational and health outcomes in older adults due to their vulnerability to circadian and sleep disruption. [ABSTRACT FROM AUTHOR]

Perinatal light exposure predisposes towards health and behaviour in adulthood. Season of birth is associated with psychiatric, allergic, cardiovascular and metabolic problems. It has been proposed that early-life environmental light disrupts the development of biological rhythms which, in turn, influence later-life health. However, the mechanisms linking perinatal seasonal light to later-life biological rhythm and health in humans are unknown. In this study, we investigated the association between season of birth and epigenome-wide DNA methylation of two postmortem human brain regions (16 hypothalamus, 14 temporal cortex). We did not find statistically significant differences at the whole epigenome level, either because we lacked statistical power or that no association exists. However, when we examined 24 CpG sites that had the highest significance or differential methylation, we identified regions which may be associated with circadian rhythm entrainment, cholinergic neurotransmission and neural development. Amongst methylation of the core clock genes, we identified that hypothalamus Neuronal PAS Domain Protein 2 (NPAS2) gene has hypermethylated regions in long photoperiod-born individuals. In addition, we found nominal associations between season of birth and genes linked to chronotype and narcolepsy. Season of birth-related brain DNA methylation profile was different than a previously reported blood methylation profile, suggesting a tissue-specific mechanism of perinatal light programming. Overall, we are the first to analyse the relationship between season of birth and human brain DNA methylation. Further studies with larger sample sizes are required to confirm an imprinting effect of perinatal light on the circadian clock. [ABSTRACT FROM AUTHOR]

International evidence indicates that older people with frailty are more likely to access social care services, compared to nonfrail older people. There is, however, no robust evidence on costs of social care provided for community‐dwelling older people living with frailty in their own homes. The main objective of this study was to examine the relationship between community‐dwelling older people living with frailty, defined using the cumulative deficit model, and annual formal social care costs for the 2012–2018 period. A secondary objective was to estimate formal social care spending for every 1% reduction in the number of older people who develop frailty over 1 year. Secondary analysis of prospective cohort data from two large nationally representative community‐based cohort studies in England was performed. Respondents aged ≥75 were used in the main analysis and respondents aged 65–74 in sensitivity testing. We used regression tree modelling for formal social care cost analysis including frailty, age, gender, age at completing education and living with partner as key covariates. We employed a minimum node size stopping criteria to limit tree complexity and overfitting and applied 'bootstrap aggregating' to improve robustness. We assessed the impact of an intervention for every 1% decrease in the number of individuals who become frail over 1 year in England. Results show that frailty is the strongest predictor of formal social care costs. Mean social care costs for people who are not frail are £321, compared with £2,895 for individuals with frailty. For every 1% of nonfrail people not transitioning to frailty savings of £4.4 million in annual expenditures on formal social care in England are expected, not including expenditure on care homes. Given considerably higher costs for individuals classed as frail compared to nonfrail, a successful intervention avoiding or postponing the onset of frailty has the potential to considerably reduce social care costs. [ABSTRACT FROM AUTHOR]

Background: Frailty is associated with adverse health outcomes in people with chronic kidney disease (CKD). Evidence supporting targeted interventions is needed. This pilot randomised controlled trial (RCT) aimed to inform the design of a definitive RCT evaluating the effectiveness of a home-based exercise intervention for pre-frail and frail older adults with CKD. Methods: Participants were recruited from nephrology outpatient clinics to this two-arm parallel group mixed-methods pilot RCT. Inclusion criteria were: ≥65 years old; CKD G3b-5; and Clinical Frailty Scale score ≥4. Participants categorised as pre-frail or frail using the Frailty Phenotype were randomised to a 12-week progressive multi-component home-based exercise programme or usual care. Primary outcome measures included eligibility, recruitment, adherence, outcome measure completion and participant attrition rate. Semi-structured interviews were conducted with participants to explore trial and intervention acceptability. Results: Six hundred and sixty-five patients had an eligibility assessment with 217 (33%; 95% CI 29, 36) eligible. Thirty-five (16%; 95% CI 12, 22) participants were recruited. Six were categorised as robust and withdrawn prior to randomisation. Fifteen participants were randomised to exercise and 14 to usual care. Eleven (73%; 95% CI 45, 91) participants completed ≥2 exercise sessions/week. Retained participants completed all outcome measures (n = 21; 100%; 95% CI 81, 100). Eight (28%; 95% CI 13, 47) participants were withdrawn. Fifteen participated in interviews. Decision to participate/withdraw was influenced by perceived risk of exercise worsening symptoms. Participant perceived benefits included improved fitness, balance, strength, well-being, energy levels and confidence. Conclusions: This pilot RCT demonstrates that progression to definitive RCT is possible provided recruitment and retention challenges are addressed. It has also provided preliminary evidence that home-based exercise may be beneficial for people living with frailty and CKD. Trial registration: ISRCTN87708989; https://clinicaltrials.gov/. [ABSTRACT FROM AUTHOR]

The term "Primary age-related tauopathy" (PART) was coined in 2014 to describe the common neuropathological observation of neurofibrillary tangles without associated beta-amyloid (Aβ) pathology. It is possible for PART pathology to be present in both cognitively normal and cognitively impaired individuals. Genetically, Apolipoprotein E (APOE) ε4 has been shown to occur less commonly in PART than in Alzheimer's disease (AD). Here, we investigate the relationships between PART, AD and those pathologically normal for age, with an emphasis on APOE and cognition, using 152 selected participants from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age and the Manchester arm of the Brains for Dementia Research cohort. APOE genotype differed between PART and AD with APOE ε2 more common in the former and APOE ε4 more common in the latter. Individuals with definite PART were less likely to be cognitively impaired than those with AD and those with pathology considered pathologically normal for age. We postulate that the lack of Aβ in definite PART cases may be due either to an increased frequency of APOE ε2 or decreased frequency of APOE ε4 as their resulting protein isoforms have differing binding properties in relation to Aβ. Similarly, an increased frequency of APOE ε2 or decreased frequency of APOE ε4 may lead to decreased levels of cognitive impairment, which raises questions regarding the impact of Aβ pathology on overall cognition in elderly subjects. We suggest that it may be possible to use the increased frequency of APOE ε2 in definite PART to assist neuropathological diagnosis. [ABSTRACT FROM AUTHOR]

If later time points had been available, a more severe decline in MC scores in AD compared to possible/definite PART would have been anticipated as the rate of both A and tau pathology accelerates compared to PART. This early detectable difference in cognition however is transient, being overcome by onset and progression of A and tau pathology in AD and possible PART, and tau pathology in definite PART. AD pathology, as measured by Braak stage, Thal phase and CERAD score, also correlated with MC test scores at time point 2. [Extracted from the article]

Objectives: Accumulating evidence points to a relationship between hearing function and cognitive ability in later life. However, the exact mechanisms of this relationship are still unclear. This study aimed to characterise latent cognitive trajectories in recall memory and identify their association with subsequent risk of hearing impairment. Methods: We analysed data from the English Longitudinal Study of Ageing Wave 1 (2002/03) until Wave 7 (2014/15). The study population consisted of 3,615 adults aged 50+ who participated in the first wave of the English Longitudinal Study of Ageing, who had no self-reported hearing impairment in Wave 1, and who underwent a hearing test in Wave 7. Respondents were classified as having hearing impairment if they failed to hear tones quieter than 35 dB HL in the better ear. Results: The trajectories of recall memory scores were grouped using latent class growth mixture modelling and were related to the presence of hearing impairment in Wave 7. Models estimating 1-class through 5-class recall memory trajectories were compared and the best-fitting models were 4-class trajectories. The different recall memory trajectories represent different starting points and mean of the memory scores. Compared to respondents with the highest recall memory trajectory, other trajectories were increasingly likely to develop later hearing impairment. Conclusions: Long-term changes in cognitive ability predict hearing impairment. Further research is required to identify the mechanisms explaining the association between cognitive trajectories and hearing impairment, as well as to determine whether intervention for maintenance of cognitive function also give benefit on hearing function among older adults. [ABSTRACT FROM AUTHOR]

The relationships between older age and sleep efficiency have traditionally been assessed using cross‐sectional studies that ignore changes within individuals as they age. This research examines the determinants of sleep efficiency, the heterogeneity in an individual's sleep efficiency trajectory across a period of up to 27 years in later life and its associations with health. The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age cohort (n = 6,375; age 42–94 years) was used in this study. Depression and health data were collected using self‐report validated instruments (Cornell Medical Index, Beck Depression Inventory and Geriatric Depression Scale). Longitudinal sleep and sociodemographic data were collected using a study‐specific self‐report questionnaire. A mixed‐effect model was performed for sleep efficiency with adjustments for time‐invariant and time‐variant predictors. Latent class analysis was used to demonstrate subgroups of sleep efficiency trajectories and associations between sleep efficiency clusters and health history of the participants were investigated. Older adults have decreased sleep efficiency over time, with 18.6% decline between 40 and 100 years of age. Three sleep efficiency trajectory clusters were identified: high (32%), medium (50%) and low sleep efficiency (18%). Belonging to the high sleep efficiency cluster was associated with having lower prevalence of hypertension, circulatory problems, general arthritis, breathing problems and recurrent episodes of depression compared to the low efficiency cluster. Overall, ageing decreases sleep efficiency. However, there are detectable subgroups of sleep efficiency that are related to prevalence of different diseases. [ABSTRACT FROM AUTHOR]

Evening-oriented sleep timing preferences have been associated with risk of diabetes, cardiovascular diseases, obesity, psychiatric disorders, and increased mortality. This research aims to explore the relationship between diurnal preferences (chronotype), daily habits, metabolic health, and mortality, using longitudinal data from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age (6375 participants at inception, recruited in the North of England) with a long follow-up period (up to 35.5 years). Mixed models were used to investigate the influence of aging, socio-demographic, and seasonal factors on sleep timing. Results show that sleep timing shifted towards earlier time with aging. Test seasons influence chronotype of older adults but working schedules challenge seasonality of sleep timing. Moreover, the season of birth may set chronotype in adulthood. Individual chronotype trajectories were clustered using latent class analysis and analyzed against metabolic health and mortality. We observed a higher risk of hypertension in the evening-type cluster compared to morning-type individuals (Odds ratio = 1.88, 95%CI = 1.02/3.47, p =.04). Evening-type cluster was also associated with traits related to lower health such as reduced sport participation, increased risk of depression and psychoticism personality, late eating, and increased smoking and alcohol usage. Finally, Cox regression of proportional hazards was used to study the effects of chronotype on longevity after adjusting for sleep duration, age, gender, smoking, alcohol usage, general health, and social class. The survival analysis (82.6% censored by death) revealed that evening-type chronotype increased the likelihood of mortality (Hazard ratio = 1.15, 95%CI = 1.04/1.26, p =.005). Taken together, chronotype is influenced by aging and seasonal effects. Evening-type preference may have detrimental outcomes for human well-being and longevity. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the association between self‐reported urinary incontinence (UI) and sexual health in a representative sample of older people. Subjects and Methods: Participants were community‐dwelling women and men aged 50–90+ years from the English Longitudinal Study of Ageing (ELSA) who reported any sexual activity in the last year. The prevalence of UI was assessed both cross‐sectionally (ELSA Wave 6; 2012) and retrospectively over the preceding 8 years (ELSA Waves 2–6; 2004–2012). Sexual activities, difficulties and concerns were assessed using a validated Sexual Relationships and Activities Questionnaire. The association between UI and sexual health outcomes was examined using weighted logistic regressions, with adjustments made for demographic, health, and lifestyle factors. Results: At Wave 6, 391 (20.0%) women and 141 (6.9%) men reported ‘any UI’ in the last 12 months. Compared to those without UI, women with UI reported declines in sexual activity and arousal over the last year, and increased concern about their frequency of sexual activity and ability to become sexually aroused. Men with ‘any UI’ reported declines in sexual desire, increased erectile and orgasm difficulties, and were more concerned about these sexual functions compared to men without UI. Differences in the patterns of association with sexual health were seen, dependent upon whether UI was reported as sporadic or persistent, and also with respect to the duration of retrospectively reported UI. Conclusion: Self‐reported UI was associated with impairment in sexual health in women and men, and mainly linked to recent declines in sexual activity and function along with elevated sexual concerns. Our findings highlight that the sexual health of older people should be considered when managing UI. [ABSTRACT FROM AUTHOR]

Introduction: highly prevalagent hearing and vision sensory impairments among older people may contribute to the risk of cognitive decline and pathological impairments including dementia. This study aims to determine whether single and dual sensory impairment (hearing and/or vision) are independently associated with cognitive decline among older adults and to describe cognitive trajectories according to their impairment pattern. Material and methods: we used data from totals of 13,123, 11,417 and 21,265 respondents aged 50+ at baseline from the Health and Retirement Study (HRS), the English Longitudinal Study of Ageing (ELSA) and the Survey of Health, Ageing and Retirement in Europe (SHARE), respectively. We performed growth curve analysis to identify cognitive trajectories, and a joint model was used to deal with attrition problems in longitudinal ageing surveys. Results: respondents with a single sensory impairment had lower episodic memory score than those without sensory impairment in HRS (β = -0.15, P < 0.001), ELSA (β = -0.14, P < 0.001) and SHARE (β = -0.26, P < 0.001). The analysis further shows that older adults with dual sensory impairment in HRS (β = -0.25, P < 0.001), ELSA (β = -0.35, P < 0.001) and SHARE (β = -0.68, P < 0.001) remembered fewer words compared with those with no sensory impairment. The stronger associations between sensory impairment and lower episodic memory levels were found in the joint model which accounted for attrition. Conclusions: hearing and/or vision impairments are a marker for the risk of cognitive decline that could inform preventative interventions to maximise cognitive health and longevity. Further studies are needed to investigate how sensory markers could inform strategies to improve cognitive ageing. [ABSTRACT FROM AUTHOR]

Background: frailty is associated with an increased risk of fragility fractures. Less is known, however, about the association between frailty and bone health. Methods: men aged 40-79 years were recruited from population registers in eight European centres for participation in the European Male Aging Study. Subjects completed a comprehensive assessment which included quantitative ultrasound (QUS) scan of the heel (Hologic-SAHARA) and in two centres, dual-energy bone densitometry (dual-energy x-ray absorptiometry, DXA). Frailty was defined based on an adaptation of Fried's phenotype criteria and a frailty index (FI) was constructed. The association between frailty and the QUS and DXA parameters was determined using linear regression, with adjustments for age, body mass index and centre. Results: in total, 3,231 subjects contributed data to the analysis. Using the Fried categorisation of frailty, pre-frail and frail men had significantly lower speed of sound (SOS), broadband ultrasound attenuation (BUA) and quantitative ultrasound index (QUI) compared to robust men (P < 0.05). Similar results were seen using the FI after categorisation into 'high', 'medium' and 'low' levels of frailty. Using the Fried categorisation, frail men had lower femoral neck bone mineral density (BMD) compared to robust men (P < 0.05), but not lower lumbar spine BMD. Using the FI categorisation, a 'high' level of frailty (FI > 0.35) was associated with lower lumbar spine BMD (P < 0.05) when compared to those with low (FI < 0.2), but not lower femoral neck BMD. When analysed as a continuous variable, higher FI was linked with lower SOS, BUA and QUI (P < 0.05). Conclusions: optimisation of bone health as well as prevention of falls should be considered as strategies to reduce fractures in frail older people. [ABSTRACT FROM AUTHOR]

We describe levels of sexual activity, problems with sexual functioning, and concerns about sexual health among older adults in the English Longitudinal Study of Ageing (ELSA), and associations with age, health, and partnership factors. Specifically, a total of 6,201 core ELSA participants (56 % women) aged 50 to >90 completed a comprehensive Sexual Relationships and Activities questionnaire (SRA-Q) included in ELSA Wave 6 (2012/13). The prevalence of reporting any sexual activity in the last year declined with age, with women less likely than men at all ages to report being sexually active. Poorer health was associated with lower levels of sexual activity and a higher prevalence of problems with sexual functioning, particularly among men. Difficulties most frequently reported by sexually active women related to becoming sexually aroused (32 %) and achieving orgasm (27 %), while for men it was erectile function (39 %). Sexual health concerns most commonly reported by women related to their level of sexual desire (11 %) and frequency of sexual activities (8 %). Among men it was level of sexual desire (15 %) and erectile difficulties (14 %). While the likelihood of reporting sexual health concerns tended to decrease with age in women, the opposite was seen in men. Poor sexual functioning and disagreements with a partner about initiating and/or feeling obligated to have sex were associated with greater concerns about and dissatisfaction with overall sex life. Levels of sexual activity decline with increasing age, although a sizable minority of men and women remain sexually active until the eighth and ninth decades of life. Problems with sexual functioning were relatively common, but overall levels of sexual health concerns were much lower. Sexually active men reported higher levels of concern with their sexual health and sexual dissatisfaction than women at all ages. Older peoples' sexual health should be managed, not just in the context of their age, gender, and general health, but also within their existing sexual relationship. [ABSTRACT FROM AUTHOR]

Background: the term frailty refers to a condition of increased vulnerability to stressors among older people, leading to a decline in homeostatic reserve. Frailty often leads to falls, hospitalisation and mortality, hence its importance for the delivery of health care to older adults. The pathophysiological mechanisms behind frailty are not well understood, but the decreased steroid-hormone production and elevated chronic systemic inflammation of older people appear to be major contributors. Method: we used a sample of 3,160 individuals aged 50 or older from the English Longitudinal Study of Ageing and assessed their frailty status according to a Frailty Index. We selected 620 single nucleotide polymorphisms in genes involved in the steroid hormone or inflammatory pathways. We performed linear association analysis. The outcome variable was the square root transformation of the Frailty Index, with age and sex entered as covariates. Results: the strongest signal was detected in the pro-inflammatory Interleukin-18 gene (rs360722, P = 0.0021, β= -0.015). Further significant signals were observed in the Interleukin-12 (rs4679868, P= 0.0062, β= -0.008 and rs9852519, P= 0.0077, β= -0.008), low density lipoprotein receptor-related protein 1 (rs1 799986, P= 0.0065, β= -0.011) and Selectin-P (rs6131, P = 0.0097, β = -0.01) genes. None of these associations remain significant after Bonferroni correction. Conclusions: we show potential associations between genetic variants of four genes and the frailty index. These genes are involved in the cholesterol transport and inflammatory pathway and, as such, our results provide further support for the involvement of the immunological processes in frailty of the elderly. [ABSTRACT FROM AUTHOR]

Background: vitamin D deficiency has been associated with an increased risk of mortality, but whether this relationship is causal or linked to co-existent comorbidity and adverse life factors remains uncertain. Our objective was to determine whether endogenous 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and parathyroid hormone (PTH) levels predicted all-cause, cardiovascular and cancer mortality independently of health and lifestyle factors.Setting: prospective cohort analysis within the European Male Ageing Study.Participants: 2,816 community-dwelling men aged 40–79 years at baseline.Methods: Cox regression was used to examine the association of all-cause mortality with 25(OH)D, 1,25(OH)2D and PTH; cardiovascular and cancer mortality were modelled using competing-risks regression. Results were expressed as hazard ratios (HR) and 95% confidence intervals (CIs) for Cox models; sub-hazard ratios (SHR) and 95% CIs for competing-risks models.Results: a total of 187 men died during a median of 4.3 years of follow-up. Serum levels of 25(OH)D (per 1 SD decrease: HR = 1.45; 95% CI = 1.16, 1.81) and 1,25(OH)2D (per 1 SD decrease: HR = 1.20; 95% CI = 1.00, 1.44) were associated with an increased risk of all-cause mortality after adjusting for age, centre, smoking, self-reported morbidities, physical activity and functional performance. Only levels of 25(OH)D <25 nmol/l predicted cancer mortality (SHR = 3.33; 95% CI = 1.38, 8.04).Conclusion: lower 25(OH)D and 1,25(OH)2D levels independently predicted all-cause mortality in middle-aged and older European men. Associations with cancer mortality were only observed among men with very low levels of 25(OH)D. These associations were only partially explained by the range of adverse health and lifestyle factors measured here. [ABSTRACT FROM AUTHOR]

Background: the link between the vitamin D endocrine axis and frailty remains undefined, with few studies examining the joint effect of vitamin D and parathyroid hormone (PTH) levels. Our objective was to determine the association of frailty with serum 25-hydroxyvitamin D (25(OH)D) and PTH.Setting: cross-sectional analysis within the European Male Ageing Study (EMAS).Participants: a total of 1,504 community-dwelling men aged 60–79 years.Methods: frailty was classified using a frailty phenotype (FP) and frailty index (FI). The association of frailty with 25(OH)D and PTH was examined using multinomial logistic regression; individual FP criteria with 25(OH)D and PTH using binary logistic regression. Results were expressed as relative odds ratios (ROR) and 95% confidence intervals (CIs) for multinomial; odds ratios (OR) and 95% CIs for binary models.Results: using the FP, 5.0% of subjects were classified as frail and 36.6% as prefrail. Lower levels of 25(OH)D were associated with being prefrail (per 1 SD decrease: ROR = 1.45; 95% CI: 1.26–1.67) and frail (ROR = 1.89; 95% CI: 1.30–2.76), after adjusting for age, centre and health and lifestyle confounders (robust group = base category). Higher levels of PTH were associated with being frail after adjustment for confounders (per 1 SD increase: ROR = 1.24; 95% CI: 1.01–1.52). Comparable results were found using the FI. Among the five FP criteria only sarcopenia was not associated with 25(OH)D levels, while only weakness was associated with PTH.Conclusion: lower 25(OH)D and higher PTH levels were positively associated with frailty in older men. Prospective data would enable the temporal nature of this relationship to be explored further. [ABSTRACT FROM PUBLISHER]

Cognitive ability has a substantial genetic component and more than 15 candidate genes have been identified over the past 8 years. One gene that has been associated with general cognitive ability is the cholinergic muscarinic 2 receptor ( CHRM2). In an attempt to replicate this finding we typed marker rs8191992 (the originally reported CHRM2 SNP) in two population based cohorts—one Scottish aged over 50 years ( N = 2,091) and the other English comprising non-demented elderly participants ( N = 758)—and a family-based Australian adolescent sample ( N = 1,537). An additional 29 SNPs in CHRM2 were typed in the Australian sample and a further seven in the English cohort. No significant association was found between CHRM2 and diverse measures of cognitive ability in any of the samples. In conclusion, this study does not support a role for CHRM2 in cognitive ability. [ABSTRACT FROM AUTHOR]

Background: Previous studies have summarized evidence on health-related quality of life for older people, identifying a range of measures that have been validated, but have not sought to present results by degree of frailty. Furthermore, previous studies did not typically use quality-of-life measures that generate an overall health utility score. Health utility scores are a necessary component of quality-adjusted life-year calculations used to estimate the cost-effectiveness of interventions.Methods: We calculated normative estimates in mean and standard deviation for EQ-5D-5L, short-form 36-item health questionnaire in frailty (SF-36), and short-form 6-dimension (SF-6D) for a range of established frailty models. We compared response distributions across dimensions of the measures and investigated agreement using Bland-Altman and interclass correlation techniques.Results: The EQ-5D-5L, SF-36, and SF-6D scores decrease and their variability increases with advancing frailty. There is strong agreement between the EQ-5D-5L and SF-6D across the spectrum of frailty. Agreement is lower for people who are most frail, indicating that different components of the 2 instruments may have greater relevance for people with advancing frailty in later life. There is a greater risk of ceiling effects using the EQ-5D-5L rather than the SF-6D.Conclusions: We recommend the SF-36/SF-6D as an appropriate measure of health-related quality of life for clinical trials if fit older people are the planned target. In trials of interventions involving older people with increasing frailty, we recommend that both the EQ-5D-5L and SF36/SF6D are included, and are used in sensitivity analyses as part of cost-effectiveness evaluation. [ABSTRACT FROM AUTHOR]

Introduction We previously reported that in male patients consulting for sexual dysfunction, low prolactin ( PRL) levels were associated with metabolic syndrome ( MetS), arteriogenic erectile dysfunction, and incident major cardiovascular events. Aim The aim of this study is to assess the clinical associations of PRL levels in the European Male Ageing Study ( EMAS). Methods EMAS is a prospective, observational cohort of community-dwelling men aged 40-79 years old (mean age 60 ± 11 years old). PRL was available for 2,948 men. Main Outcome Measures Different parameters were evaluated including the Short Form-36 questionnaire, Becks Depression Inventory, the Adverse Life Events Scale, the Physical Activity Scale for the Elderly, and the EMAS sexual function questionnaire ( EMAS-SFQ). Results After the adjustment for confounders, PRL levels were inversely related with worsening of sexual function as compared with the previous year, as derived from change in sexual functioning domain of the EMAS-SFQ (adj. r = −0.043; P = 0.029). The strongest correlation ( Wald = 6.840; P = 0.009) was observed between lower PRL levels and reduced enjoyment of orgasmic experiences. Furthermore, an inverse relationship between PRL levels and stressful life events or depressive symptoms was observed. Low PRL was also negatively associated with an unhealthy metabolic phenotype as well as with the MetS (Wald = 5.229; P = 0.022). In line with these data, low PRL was associated with a lower level of physical activity and feeling unhealthier. Conclusions Low PRL is related to several metabolic, psychological, and sexual unhealthy characteristics in European men. Checking PRL might be useful to stratify men for cardiovascular risk and to encourage appropriate lifestyle changes. Corona G, Wu FC, Rastrelli G, Lee DM, Forti G, O'Connor DB, O'Neill TW, Pendleton N, Bartfai G, Boonen S, Casanueva FF, Finn JD, Huhtaniemi IT, Kula K, Punab M, Vanderschueren D, Rutter MK, Maggi M, and the EMAS Study Group. Low prolactin is associated with sexual dysfunction and psychological or metabolic disturbances in middle aged and elderly men: The European Male Aging Study (EMAS). J Sex Med 2014;11:240-253. [ABSTRACT FROM AUTHOR]

Abstract: Objective: For older people who have had hip fracture surgery, to evaluate the cost-effectiveness of a nurse-led intervention in treating depression compared to treatment as usual (TAU), and to evaluate the cost-effectiveness of a psychological treatment for the prevention of depression. Design: Two linked cost-effectiveness studies for the treatment and prevention of depression after hip surgery, from the perspective of health, social care, voluntary sector agencies and unpaid carers. Setting: Orthopaedic units in Manchester, England. Participants: One hundred and twenty-one patients with Geriatric Depression Scale (GDS) scores greater than 6 were included in the treatment study and 172 patients with GDS scores less than or equal to 6 were enrolled in the prevention study. Interventions: Nurse-led intervention for treating depression versus TAU; and cognitive behaviour therapy (CBT) for preventing depression following surgery for hip fracture. Main outcome measures: Outcomes were changes in HADS-depression scores at 6weeks. Costs covered treatment and all service impacts. Results: After 6weeks, there were no significant differences in cost. However, the nurse-led intervention group had a lower mean HADS-depression score compared to TAU. In the prevention study, there were no significant differences in cost and depression score between patients treated with CBT and TAU. Conclusion: The results for this parallel randomized controlled study show that after hip fracture surgery a nurse-led intervention may be a cost-effective option for the treatment of depression in older people with depression. However CBT does not appear to be a cost-effective option for the prevention of depression in this population. [ABSTRACT FROM AUTHOR]